LYMPHOCYTES SELECTED IN ALLOGENEIC THYMIC EPITHELIUM MEDIATE DOMINANTTOLERANCE TOWARD TISSUE GRAFTS OF THE THYMIC EPITHELIUM HAPLOTYPE

Athymic mice grafted at birth with allogeneic thymic epithelium (TE) f rom day 10 embryos before hematopoietic cell colonization reconstitute normal numbers of T cells and exhibit full life-long tolerance to ski n grafts of the TE haplotype. Intravenous transfers of splenic cells, from these animals to adult syngeneic athymic recipients, reconstitute T-cell compartments and the ability to reject third-party skin grafts . The transfer of specific tolerance to skin grafts of the TE donor st rain, however, is not observed in all reconstituted recipients, and th e fraction of nontolerant recipients increases with decreasing numbers of cells transferred. Furthermore, transfers of high numbers of total or CD4(+) T cells from TE chimeras to T-cell receptor-anti-H-Y antige n transgenic immunocompetent syngeneic hosts specifically hinder the r ejection of skin grafts of the TE haplotype that normally occurs in su ch recipients. These observations demonstrate (i) that mice tolerized by allogeneic TE and bearing healthy skin grafts harbor peripheral imm unocompetent T cells capable of rejecting this very same graft; and (i i) that TE selects for regulatory T cells that can inhibit effector ac tivities of graft-reactive cells.